Tandem mass spectrometry techniques typically involve the detection of ions that have undergone physical change(s) in a mass spectrometer. Frequently, the physical change involves dissociating or fragmenting a selected precursor or parent ion and recording the mass spectrum of the resultant fragment or child ions. The information in the fragment ion mass spectrum is often a useful aid in elucidating the structure of the precursor or parent ion. For example, the general approach used to obtain a mass spectrometry/mass spectrometry (MS/MS or MS2) spectrum is to isolate a selected precursor or parent ion with a suitable m/z analyzer, subject the precursor or parent ion to energetic collisions with a neutral gas in order to induce dissociation, and finally to mass analyze the fragment or child ions in order to generate a mass spectrum.
An additional stage of MS can be applied to the MS/MS scheme outlined above, giving MS/MS/MS or MS3. This additional stage can be quite useful to elucidate dissociation pathways, particularly if the MS2 spectrum is very rich in fragment ion peaks or is dominated by primary fragment ions with little structural information. MS3 offers the opportunity to break down the primary fragment ions and generate additional or secondary fragment ions that often yield the information of interest. Indeed, the technique can be carried out n times to provide an MSn spectrum.
Ions are typically fragmented or dissociated in some form of a collision cell where the ions are caused to collide with an inert gas. Dissociation is induced either because the ions are injected into the cell with a high axial energy or by application of an external excitation. See, for example, WIPO publication WO00/33350 dated Jun. 8, 2000 by Douglas et al.
Douglas discloses a triple quadrupole mass spectrometer wherein the middle quadrupole is configured as a relatively high-pressure collision cell in which ions are trapped. This offers the opportunity to both isolate and fragment a chosen ion using resonant excitation techniques. The problem with the Douglas system is that the ability to isolate and fragment a specific ion within the collision cell is relatively low. To compensate for this, Douglas uses the first quadrupole as a mass filter to provide high resolution in the selection of precursor ions, which enables an MS2 spectrum to be recorded with relatively high accuracy. However, to produce an MS3 (or higher) spectrum, isolation and fragmentation must be carried out in the limited-resolution collision cell.